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Updated: Jan 22, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Mannose Receptor-positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic
Jelani C Zarif1, Javier A Baena-Del Valle2, Jessica L Hicks3
1The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Background:
M2 tumor-associated macrophages (M2-TAMs) can suppress inflammation in the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported M2-TAM infiltration in metastatic castration-resistant prostate cancer (mCRPC).
Objective:
To determine whether the extent of M2-TAM infiltration correlates with PC aggressiveness.
Design, Setting, And Participants:
Normal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed.
Outcome Measurements And Statistical Analysis:
We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement.
Results And Limitations:
Multiplex immunofluorescent staining showed that a small fraction of CD206 staining co-localized with the endothelial cells of lymphatic vessels, while the vast majority of staining occurred in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion from normal (ie, no inflammation) prostate tissue, to primary untreated carcinomas, to hormone-naïve regional lymph node metastases, to mCRPC. Complementary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Limitations include the small number of rapid autopsy samples and the lack of neuroendocrine PC samples.
Conclusions:
Our results revealed a progressive increase in CD206-positive macrophages from normal prostate to mCRPC. Given the immunosuppressive nature of macrophages and the lack of clinical success of immunotherapy for PC patients, our results provide a rationale for therapeutic targeting of macrophages in the PC microenvironment as a potential method to augment immunotherapeutic responses.
Patient Summary:
In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.
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